Project description
Molecular control of self-tolerance to nucleic acids in innate immunity
The recognition of nucleic acids allows the detection of diverse pathogens by a limited number of innate immune receptors but increases the threat of a potential autoimmune response. Toll-like receptors (TLR) TLR7 and TLR9 can recognise self RNA or DNA and contribute to autoimmune diseases. It is therefore important to define their subcellular localisation and learn how they are coordinated in time to fully understand TLR regulation and avoid self-recognition. The EU-funded TLRstorm project aims to investigate fundamental aspects of TLR biology. State-of-the-art sub-diffraction imaging techniques will provide insight into the spatial and temporal control of TLR signalling and help us define the molecular principles that maintain self-tolerance to nucleic acids.
Objective
Recognition of nucleic acids enables detection of diverse pathogens by a limited number of innate immune receptors, but also exposes the host to potential autoimmunity. At least two members of the Toll-like receptor (TLR) family, TLR7 and TLR9, can recognize self-RNA or DNA, respectively, and contribute to the pathology of autoimmune diseases. Despite the structural and functional similarities between these two receptors, they can have opposing effects in autoimmune diseases such as systemic lupus erythematosus. My previous studies have identified a potential explanation for this enigma, whereby TLR7 and TLR9 experience a surprising degree of differential regulation, both at the level of receptor trafficking as well as receptor activation in the endosome. Although my work provides a major conceptual advance for explaining the distinct behavior of these two receptors in disease, we still poorly understand how the regulation of nucleic acid-sensing TLRs and its various interactions and pathways are embedded into the cellular architecture. Their cellular location is not trivial: knowing where in the cell these critical interactions take place and how they are coordinated in time is of utmost importance to fully understand how TLRs are regulated to avoid self-recognition. In this project, I aim to investigate these fundamental aspects of TLR biology using state-of-the art superresolution microscopy. I will use sub-diffraction imaging techniques including stochastic optical reconstruction microscopy (STORM) and Airyscanning technology to 1) define the precise subcellular localization of nucleic acid-sensing TLRs, 2) identify and characterize their endosomal signaling compartments, and 3) investigate TLR signaling dynamics under normal and autoimmune-prone conditions. This work will provide a conceptual framework for understanding how TLR signaling is controlled in space and time and define the molecular principles that maintain self-tolerance to nucleic acids.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules nucleic acids
- natural sciences physical sciences optics microscopy super resolution microscopy
- social sciences sociology social issues social inequalities
- medical and health sciences basic medicine immunology autoimmune diseases
- medical and health sciences basic medicine pathology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2018
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
14195 Berlin
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.